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https://www.readbyqxmd.com/read/29149720/a-robust-strategy-for-preparation-of-sequential-stimuli-responsive-block-copolymer-prodrugs-via-thiolactone-chemistry-to-overcome-multiple-anticancer-drug-delivery-barriers
#1
Wendong Ke, Wei Yin, Zengshi Zha, Jean Felix Mukerabigwi, Weijian Chen, Yuheng Wang, Chuanxin He, Zhishen Ge
Block copolymer prodrugs (BCPs) have attracted considerable attentions in clinical translation of nanomedicine owing to their self-assembly into well-defined core-shell nanoparticles for improved pharmacokinetics, stability in blood circulation without drug leakage, and optimized biodistribution. However, a cascade of physiological barriers against specific delivery of drugs into tumor cells limit the final therapeutic efficacy. Herein, we report a robust and facile strategy based on thiolactone chemistry to fabricate well-defined BCPs with sequential tumor pH-promoted cellular internalization and intracellular stimuli-responsive drug release...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29149681/mechanistic-insight-into-contextual-tgf-%C3%AE-signaling
#2
REVIEW
Ying E Zhang
Transforming growth factor-β (TGF-β) controls a wide range of cellular functions by activating both SMADs and non-SMAD pathways. In different tissue or physiological environment, cellular responses to TGF-β can be diverse, even opposite. Complex regulations at the level of ligand mobilization, receptor presentation, and the network of intracellular signal transducers afford the TGF-β pathway with versatile means to induce precise cellular responses in accordance to specific contextual demands. This article summarizes recent development in how cells manage their responses to TGF-β through ligand activation, receptor abundance, as well as SMAD-dependent and SMAD-independent mechanisms...
November 14, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29149547/engineering-escherichia-coli-co-cultures-for-production-of-curcuminoids-from-glucose
#3
Zhen Fang, J Andrew Jones, Jingwen Zhou, Mattheos A G Koffas
Curcuminoids have attracted increasing attention because of the antioxidant, anticancer, and antitumor activities while their production is limited because of its main source, turmeric plant, demonstrates extensive seasonal variation. In this study, we constructed Escherichia coli co-culture system for the rapid production of curcuminoids from glucose. Firstly, the overexpression of curcuminoid synthase and four different strategies related to increasing the intracellular malonyl-CoA pool were conducted in engineered E...
November 17, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29149416/history-of-histamine-releasing-factor-hrf-translationally-controlled-tumor-protein-tctp-including-a-potential-therapeutic-target-in-asthma-and-allergy
#4
Susan M MacDonald
Histamine-releasing factor (HRF) also known as translationally controlled tumor protein (TCTP) is a highly conserved, ubiquitous protein that has both intracellular and extracellular functions. Here we will highlight the subcloning of the molecule, its clinical implications, as well as an inducible-transgenic mouse. Particular attention will be paid to its extracellular functioning and its potential role as a therapeutic target in asthma and allergy. The cells and the cytokines that are produced when stimulated or primed by HRF/TCTP will be detailed as well as the downstream signaling pathway that HRF/TCTP elicits...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149324/pyrethroid-insecticide-cypermethrin-modulates-gonadotropin-synthesis-via-calcium-homeostasis-and-erk1-2-signaling-in-l%C3%AE-t2-mouse-pituitary-cells
#5
Feixue Li, Huihui Ma, Jing Liu
Pyrethroids are a class of widely used insecticides. Cypermethrin (CP) is one of most commonly used pyrethroid insecticides and its residue has been frequently detected in environmental media. Our recent animal study reported that early postnatal exposure to CP induced an increase in serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as well as the expression of gonadotropin subunit genes [chorionic gonadotropin α (CGα), LHβ and FSHβ] in pituitary tissues. In this study, we further investigated the precise mechanism by which CP at concentrations of 1-100 nM affected the synthesis of gonadotropins using a murine pituitary gonadotropic cell line LβT2...
November 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29149297/dna-knots-occur-in-intracellular-chromatin
#6
Antonio Valdés, Joana Segura, Sílvia Dyson, Belén Martínez-García, Joaquim Roca
In vivo DNA molecules are narrowly folded within chromatin fibers and self-interacting chromatin domains. Therefore, intra-molecular DNA entanglements (knots) might occur via DNA strand passage activity of topoisomerase II. Here, we assessed the presence of such DNA knots in a variety of yeast circular minichromosomes. We found that small steady state fractions of DNA knots are common in intracellular chromatin. These knots occur irrespective of DNA replication and cell proliferation, though their abundance is reduced during DNA transcription...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29149261/glut10-maintains-the-integrity-of-major-arteries-through-regulation-of-redox-homeostasis-and-mitochondrial-function
#7
Yu-Wei Syu, Hao-Wen Lai, Chung-Lin Jiang, Hong-Yuan Tsai, Chung-Chih Lin, Yi-Ching Lee
Glucose transporter 10 (GLUT10) is a member of the GLUT family of membrane transporters, and mutations in this gene cause arterial tortuosity syndrome (ATS). However, the physiological role and regulation of GLUT10 in arteries remains unclear. To further understand its physiological roles in major arteries, we examined the regulatory mechanisms of GLUT10 in ASMCs and aortic tissues. Interestingly, we find that targeting of GLUT10 to mitochondria is increased in ASMCs under both stress and aging conditions, which enhances dehydroascorbic acid (DHA) uptake and maintains intracellular ascorbic acid (AA) levels...
November 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29149100/bcl-2-family-proteins-changing-partners-in-the-dance-towards-death
#8
REVIEW
Justin Kale, Elizabeth J Osterlund, David W Andrews
The BCL-2 family of proteins controls cell death primarily by direct binding interactions that regulate mitochondrial outer membrane permeabilization (MOMP) leading to the irreversible release of intermembrane space proteins, subsequent caspase activation and apoptosis. The affinities and relative abundance of the BCL-2 family proteins dictate the predominate interactions between anti-apoptotic and pro-apoptotic BCL-2 family proteins that regulate MOMP. We highlight the core mechanisms of BCL-2 family regulation of MOMP with an emphasis on how the interactions between the BCL-2 family proteins govern cell fate...
November 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29149079/sphingosine-1-phosphate-s1p-signaling-in-glioblastoma-multiforme-a-systematic-review
#9
REVIEW
Shailaja Mahajan-Thakur, Sandra Bien-Möller, Sascha Marx, Henry Schroeder, Bernhard H Rauch
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29148970/autophagic-cell-death-is-dependent-on-lysosomal-membrane-permeability-through-bax-and-bak
#10
Jason Karch, Tobias G Schips, Bryan D Maliken, Matthew J Brody, Michelle A Sargent, Onur Kanisciak, Jeffery D Molkentin
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and in a previous eLIFE paper, Karch et al., 2013 showed that these 2 effectors are also needed for mitochondrial-dependent cellular necrosis. Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29148820/a-functional-kinase-short-interfering-ribonucleic-acid-screen-using-protease-activated-receptor-2-dependent-opening-of-transient-receptor-potential-vanilloid-4
#11
William G Darby, Megan S Grace, Kaylene J Simpson, Owen L Woodman, Peter McIntyre
Protease-activated receptor 2 (PAR2) is a proinflammatory G-protein coupled receptor (GPCR) that is activated by inflammatory proteases, and its activation initiates signaling pathways that modulate the nonselective cation channel transient receptor potential vanilloid-4 (TRPV4). PAR2-dependent opening of TRPV4 has been attributed to kinase activation, but the identity of the responsible enzymes is unknown. Deciphering the signaling pathways involved in the PAR2-dependent opening of TRPV4 may yield new targets for pain treatment...
November 17, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29148036/function-and-mechanism-of-the-pyrin-inflammasome
#12
REVIEW
Rosalie Heilig, Petr Broz
Pyrin, encoded by the MEFV gene, is an intracellular pattern recognition receptor that assembles inflammasome complexes in response to pathogen infections. Mutations in the MEFV gene have been linked to autoinflammatory diseases such as Familial Mediterranean Fever (FMF) or pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Recent insights have now revealed how pyrin is activated during infection, providing a molecular basis for the understanding of such disease-causing mutations in pyrin...
November 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29147902/expression-of-dj-1-in-cancer-cells-its-correlation-with-clinical-significance
#13
Takahiko Kawate, Benio Tsuchiya, Keiichi Iwaya
Upregulation of DJ-1 mRNA is commonly observed in various human cancers such as ductal carcinoma of the breast, non-small cell carcinoma of the lung, pancreatic duct adenocarcinoma, urinary transitional cell carcinoma, and gynecologic carcinoma. At the protein level, intensity and intracellular localization of DJ-1 expression is varied, and the DJ-1 protein regulates cancer progression, clinical aggressiveness, differentiation, cancer cell morphology, and drug sensitivity. Thus, DJ-1 plays a critical role in cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147891/long-term-presence-of-angiotensin-ii-type-1-receptor-autoantibody-reduces-aldosterone-production-by-triggering-ca-2-overload-in-h295r-cells
#14
Jinghui Lei, Suli Zhang, Pengli Wang, Yang Liao, Jingwei Bian, Xiaochen Yin, Ye Wu, Lina Bai, Feng Wang, Xiaoli Yang, Huirong Liu
Preeclamptic women are reported to have inadequate plasma volume expansion coupled with a suppressed secretion of aldosterone; however, the specific mechanism of preeclampsia remains unclear. We demonstrated that the presence of long-term angiotensin II type 1 receptor autoantibody (AT1-AA) reduces aldosterone production by triggering a Ca(2+) overload in H295R cells. AT1-AA was discovered in preeclamptic women and reported to activate AT1R, and consequently elevate intracellular Ca(2+). We found that AT1-AA significantly prolonged the time of intracellular Ca(2+) elevation...
November 16, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29147733/-inhibitors-of-the-androgen-receptor-n%C3%A2-terminal-domain-therapies-targeting-the-achilles-heel-of-various-androgen-receptor-molecules-in-advanced-prostate-cancer
#15
REVIEW
M C Hupe, A Offermann, F Perabo, C Chandhasin, S Perner, A S Merseburger, M V Cronauer
Although prostate cancer responds well to primary endocrine therapies, tumor progression with castration resistant tumor cells almost invariably occurs within a few years. Unfortunately, some CRPC patients do not respond to second-line therapies with abiraterone or enzalutamide. Moreover, patients who initially responded well to second-line hormone therapy develop resistance to abiraterone and/or enzalutamide within a short period of time. Besides an increase of intracellular androgen receptor (AR) levels, the predominant resistance mechanisms include AR aberrations (point mutations, AR splice variants) occurring predominantly at the androgen or ligand binding domain of the AR...
November 16, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29147716/complex-coacervation-of-mg-ii-phospho-polymethacrylate-a-synthetic-analog-of-sandcastle-worm-adhesive-phosphoproteins
#16
In Taek Song, Russell J Stewart
The highly phosphorylated Pc3 proteins, major components of the sandcastle worm adhesive, are sequestered with Mg as spherical sub-granules within heterogeneous secretory granules in adhesive gland cells. The phase behavior of a synthetic phospho-polymethacrylate analog of the Pc3 phosphoproteins, in the presense of Mg(ii), was characterized to determine whether it is chemically possible for the natural adhesive components to be packaged and stored as liquid complex coacervates. Of several multivalent metal salts tested, only MgCl induced complex coacervation of the phospho-copolymer...
November 17, 2017: Soft Matter
https://www.readbyqxmd.com/read/29147652/identification-of-potent-chloride-intracellular-channel-protein-1-inhibitors-from-traditional-chinese-medicine-through-structure-based-virtual-screening-and-molecular-dynamics-analysis
#17
Wei Wang, Minghui Wan, Dongjiang Liao, Guilin Peng, Xin Xu, Weiqiang Yin, Guixin Guo, Funeng Jiang, Weide Zhong, Jianxing He
Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29147545/protein-labeling-for-live-cell-fluorescence-microscopy-with-a-highly-photostable-renewable-signal
#18
Nina G Bozhanova, Mikhail S Baranov, Natalia V Klementieva, Karen S Sarkisyan, Alexey S Gavrikov, Ilia V Yampolsky, Elena V Zagaynova, Sergey A Lukyanov, Konstantin A Lukyanov, Alexander S Mishin
We present protein-PAINT - the implementation of the general principles of PAINT (Point Accumulation for Imaging in Nanoscale Topography) for live-cell protein labeling. Our method employs the specific binding of cell-permeable fluorogenic dyes to genetically encoded protein tags. We engineered three mutants of the bacterial lipocalin Blc that possess different affinities to a fluorogenic dye and exhibit a strong increase in fluorescence intensity upon binding. This allows for rapid labeling and washout of intracellular targets on a time scale from seconds to a few minutes...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147526/a-ratiometric-fluorescent-probe-for-imaging-and-quantifying-anti-apoptotic-effects-of-gsh-under-temperature-stress
#19
Xiaoyue Han, Xinyu Song, Fabiao Yu, Lingxin Chen
Hypothermia and hyperthermia are cell stressed states resulting from environmental temperature changes, which can abnormally decrease intracellular glutathione (GSH) concentrations and induce apoptosis. As the most abundant intracellular non-protein biothiol, GSH can protect cells from apoptosis. Considering the important roles of GSH in the anti-apoptotic process in cells and in vivo, we strive to develop a powerful chemical tool for the direct detection of GSH concentration changes under temperature stress...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147021/genome-scale-modeling-and-transcriptome-analysis-of-leuconostoc-mesenteroides-unravel-the-redox-governed-metabolic-states-in-obligate-heterofermentative-lactic-acid-bacteria
#20
Lokanand Koduru, Yujin Kim, Jeongsu Bang, Meiyappan Lakshmanan, Nam Soo Han, Dong-Yup Lee
Obligate heterofermentative lactic acid bacteria (LAB) are well-known for their beneficial health effects in humans. To delineate the incompletely characterized metabolism that currently limits their exploitation, at systems-level, we developed a genome-scale metabolic model of the representative obligate heterofermenting LAB, Leuconostoc mesenteroides (iLME620). Constraint-based flux analysis was then used to simulate several qualitative and quantitative phenotypes of L. mesenteroides, thereby evaluating the model validity...
November 16, 2017: Scientific Reports
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